Pathologic process in which the endothelial cell plays a key role are a leading cause of death in man. Cultured human endothelial cells (HEC) in serum-free medium will be used for long-term study of the endocrine control of growth, function and aging of the human vasculature. Two growth factors, one from neural tissue and one from liver cells, will be isolated and characterized. As much of the N-terminal amino acid sequence as possible will be determined for each factor by gas phase sequencing. Monospecific antibody and DNA probes will be prepared based on the sequencing information. These reagents will be used to isolate recombinant bacterial clones containing the cDNA coding for growth factor mRNA. The monospecific antibody and cDNA probes will be used to analyze the sites and regulation of synthesis of the two types of HEC growth factors. Primary emphasis will be on a rigorous test of the hypothesis that liver is an important endocrine organ in the biology of endothelial cells. Hepatocytes are an important source of an HEC maintenance and regeneration factor. Hormonal regulation of the synthesis and secretion of the factor in cultured liver cells will be elucidated.